Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. A better understanding of how the pathological mechanisms drive the deterioration of RA progress in individuals is urgently required in order to develop therapies that will effectively treat patients at each stage of the disease progress. Here we dissect the etiology and pathology at specific stages: (i) triggering, (ii) maturation, (iii) targeting, and (iv) fulminant stage, concomitant with hyperplastic synovium, cartilage damage, bone erosion, and systemic consequences. Modern pharmacologic therapies (including conventional, biological, and novel potential small molecule disease-modifying anti-rheumatic drugs) remain the mainstay of RA treatment and there has been significant progress toward achieving disease remission without joint deformity. Despite this, a significant proportion of RA patients do not effectively respond to the current therapies and thus new drugs are urgently required. This review discusses recent advances of our  understanding of RA pathogenesis, disease modifying drugs, and provides perspectives on next generation therapeutics for RA. The preclinical stages of rheumatoid arthritis (RA) represent a golden window for the development of therapies which could someday prevent the onset of clinical disease. The autoimmune processes underpinning RA usually begin many years before symptoms such as joint pain and stiffness emerge. Recent studies have identified some of the key cellular players driving these processes and begun to unpick how genetic and environmental risk factors combine to trigger them; they also suggest the existence of several distinct subtypes of RA, which require further exploration. Jiake Xu at the University of Western Australia in Perth and colleagues review current treatment strategies for RA and how such insights could ultimately lead to the earlier diagnosis of RA - as well as providing new opportunities for drug treatment and prevention through behavioral changes in high-risk individuals.